The problem of low peak concentration of gentamicin in clinical practice

Aminoglycoside antibiotics have particular importance in the treatment of Gram-negative infections. Toxicity of gentamicin is well-known, but patients often receive insufficient dosage in clinical practice. The purpose of this study was to refer to the problem of insufficient dosages that were confirmed by low peak concentration and to determine relationship between low peak levels and pharmacokinetic parameters, renal function and body weight.

We studied 68 patients who were treated with gentamicin for one year (August 2010 - August 2011). Therapeutic drug monitoring (TDM) was applied for all the patients. Gentamicin peak and trough concentrations were measured by the FPIA (Fluorescence Polarization Immunoassay) method with an analyser, AxSYM of ABBOTT company. We divided the patients into 3 groups according to peak and trough levels.

Together 13 (19%) patients had high trough concentrations and optimal peak concentrations. Only 6 (9%) patients had optimal trough and peak levels in the first measurement of plasma concentrations. The third group included 49 patients (72%). These patients had optimal trough levels and low peak levels in the first measurement. 34 patients of the third group (28 males, 6 females) had optimal peak levels after adjustment of dosage in the second measurement. 15 patients, only males did not reach optimal peak levels even after adjustment of dosage in the second measurement.

The patients with low peak levels of gentamicin are more frequent than patients with toxic adverse effects in clinical practice. Especially, these are the patients with higher value of body weight and following increased pharmacokinetic parameters: creatinine clearance, total volume of distribution, total clearance and elimination rate constant. The clinical pharmacists have to adjust dosage regimens, especially according to Therapeutic drug monitoring (TDM) and clinical experience. The results of the study have confirmed that the clinical pharmacists must adjust dose regimen not only for patients who require reduced doses but more often for patients who require higher doses than are commonly used in clinical practice. These patients are at risk of underdosing of aminoglycoside antibiotics.